Carbohydrate mixture

ABSTRACT

The invention relates to a carbohydrate mixture for dietetic foods administered by the enteral or parenteral route and pharmaceuticals, characterized in that said mixture consists of (a) monosaccharide(s), (b) oligosaccharide(s) (at most hexasaccharides) and (c) polysaccharide(s) (at least heptasaccharides), where the mixing ratio a, b, c, in respect of weight, is: α=1, b=40 to 1000, and c=1 to 50, and in that it contains at least 1 weight percent of fucose occurring either freely and/or bound to an oligosaccharide and/or a polysaccharide. According to the invention, the carbohydrate mixture has both a nutritional and a biological effect which is considerably greater than the corresponding action of the individual constituents.

The invention concerns a carbohydrate mixture for dietetic, enteral andparenteral foods and also pharmaceuticals, and the use of thiscarbohydrate mixture.

As is well-known, carbohydrates are one of the essential basic pillarsof the diet. Hence, a great diversity of carbohydrates are added to thea great variety of foods, in particular “artificially” produced foods,and also pharmaceuticals. The purpose of the carbohydrates here isprimarily of a nutritive nature, or they function as dietary fibre.

The carbohydrates consist of monosaccharides, or are composed of these.Depending on degree of polymerisation, the carbohydrates are describedas oligosaccharides or polysaccharides or glycans. In the context of thepresent documents, carbohydrates with up to 6 monosaccharide units areunderstood here as oligosaccharides. Carbohydrates with 7 and moremonosaccharides are referred to here as polysaccharides.

Owing to the variability of the monomers making up the carbohydrates,the position of the glycosidic bond and the anomerism of thecarbohydrates, these carbohydrates and conjugates thereof constitute anextremely heterogeneous and extensive class of substances.

Now carbohydrates have a great diversity of biological functions. Inthis connection, purely by way of example, it is mentioned that glycanstructures play an important part particularly in cell-matrix, cell-celland similar recognition and adhesion processes. The carbohydratestructures are present both as free oligosaccharides and also in boundform, for example in glycoproteins, proteoglycans and glycolipids. Theadhesion of microorganisms to glyco-structures of epithelia/endotheliaor other endogenous cells inter alia also has effects on the cellmetabolism of the host organism. Now the list of functions that areperformed by carbohydrates could be extended to any length. Theabove-described function of the glycan structures is thus only anarbitrarily chosen example.

Carbohydrates are now used increasingly in foods, “functional food” andpharmaceuticals with a biological activity in mind. Previously, however,only some specific carbohydrate species possessing a particular propertywere used.

Hence the purpose of the present invention is to provide a carbohydratemixture which can be incorporated into dietetic, enteral and parenteralfoods and also pharmaceuticals, and as well as a nutritive effect alsopossesses a broad spectrum of activity.

This purpose is achieved through the teaching of the claims.

It was surprisingly found that the biological action of the mixture ofmonosaccharides, oligosaccharides and polysaccharides according to theinvention is considerably more potent than the corresponding action ofthe individual components. Thus with the mixture according to theinvention the following biological effects can be achieved:

prevention of the adhesion of pathogenic substances/organisms such astoxins, viruses, bacteria, fungi, transformed cells and parasites

decomposition of complexes of toxins, viruses, bacteria, fungi and otherpathogens with endogenous cells and their elimination from the body

stabilisation of a natural microflora

acceleration of wound-healing (for pharmaceutical and enteral mixtures).

Thus the mixture according to the invention is suitable for theprophylaxis and/or treatment of symptoms/diseases, which are connectedwith the association/adhesion of the said substances and organisms toepithelia or other endogenous cells (such as diarrhea, meningitis,otitis, gastritis and influenza). The mixture according to the inventionadditionally has a nutritive effect owing to degradation reactions byendogenous enzymes and subsequent absorption of the products.

While the degradation rate, kinetics and absorption are relevant for thenutritive and prebiotic effects of the carbohydrate mixture according tothe invention, surprisingly not only the chemical composition but alsothe mixing ratio of monosaccharides/oligosaccharides/poly-saccharides isimportant for the biological function.

Thus, the mixing ratio of a=monosaccharide, b=oligosaccharide andc=polysaccharide according to the invention is as follows: a=1, b=40 to1000, c=1 to 50.

As oligosaccharides here, those up to hexasaccharide (e.g. mono-, di-,tri-, terra-, penta and hexasaccharide) are understood.

When in the context of the present documents a saccharide is referred toin the singular, then this can be not only a single species, but also amixture of any species. When in addition in the context of the presentdocuments ranges are referred to, then with the statement of the rangeat least all whole-number intermediate values and also narrower rangesincluded by the range are covered and disclosed. This means for examplefor the component c, which can be 1 to 50, that with this theintermediate values, such as 2, 3, 4, . . . 12, 13, 14, . . . 25, 26,27, . . . 37, 38, 39, 40, 41 . . . are also covered. The same appliesanalogously for the component b, so that with this all, at leastwhole-number, intermediate values lying between 40 to 1000 (e.g. 41, 42,43, 44 . . . up to 998, 999) are disclosed.

The mixture of the components of the carbohydrate mixture according tothe invention thus constitutes an essential feature of the invention.The mixing ratio of monosaccharides, oligosaccharides andpolysaccharides here is preferably 1:40:10 to 1:1000:1 and in particular1:80:20. In this case also, by this statement, all, particularlywhole-number, values lying between the range limits are also covered anddisclosed. Here the molecular weight of the polysaccharides can beextended to several Mda and to particular carbohydrates with a largenumber of active groups.

A further important feature of the mixture according to the inventionconsists in that at least ca. 1 wt % fucose is present in this mixture(incidentally, unless otherwise stated, all quantity statements arebased on weight). Here the fucose can be present in free form or inbound form (as fucosylated oligosaccharide or fucosylatedpolysaccharide). Naturally, it is also possible that the facose ispresent both in free form and also in bound form. Here this facosepreferably makes up at least ca. 5 wt % and in particular 5 to 10 wt %of the carbohydrate mixture according to the invention.

According to a further preferred embodiment, the carbohydrate mixtureaccording to the invention in addition contains ca. 1 wt % sialic acidHere in the context of the present documents the term sialicacid standsfor the following substances or the following substances are subsumedthereunder: N-acetyl-neuraminic acid, N-glycolyl-neuraminic acid andother neuraminic acids. All these sialic acids can also be present inO-acetylated form. Here the sialic acids can be present free or be boundto an oligosaccharide and/or to a polysaccharide. Naturally, anymixtures are also possible. Here the sialic acid preferably makes up 1to 5 wt % and is present especially as sialyllactose and/ordisialyllactose or disialyllacto-N-tetraose.

For the production of the carbohydrate mixture according to theinvention, all carbohydrates and carbohydrate mixtures previously knownand in particular used for the production of foods or foodstuffs can beused. It is also possible to use raw materials already altered bytechnical modification The production of the mixture according to theinvention can be effected by simple mixing of the appropriately selectedmonosaccharides, oligosaccharides and polysaccharides in the desiredmixing ratio.

Thus as raw materials both free carbohydrates such as storagecarbohydrates (starch, fructans) and also structural carbohydrates suchas celluloses, hemicelluloses and chitins can be used. In addition,glycoconjugates such as glycolipids, glycoproteins, proteoglycans, etc.,can be used. It is also possible to perform tan enzymatic modificationof the raw materials and products with hydrolases (for example,glycosidases, transglycosidases and lipases), transferases (for examplefucosyl-transferases and sialyltransferases), isomerases (for examplealdolases and ketolases), oxidoreductases (for example oxidases) andreductases (glucose dehydrogenase)), lyases (for example polysaccharidelyase) and ligases. Further, it is possible to perform a technicalmodification of the raw materials and products, namely by pressure (forexample extrusion), temperature (for example caramelisation), organicsyntheses, organic modification (for example carboxymethylation andperacetylation), acid and/or basic hydrolysis and fractionation (forexample on the basis of size and/or physicochemical parameters such ascharge and hydrophobicity).

Also, the carbohydrate mixture according to the invention is essentiallycomposed of the monosaccharides listed below and the oligosaccharidesand polysaccharides built up from them:

N-acetyineuramninic acid, N-glycolylneuraminic acid and/or O-acetylatedforms thereof, D-glucose, D-fructose, D-galactose, D-mannose, L-fucose,D-N-acetylglucosarnine, D-N-acetl-galactosamine, D-xylose, L-rharnnose,D-arabinose, D-allose, D-talose, D-idose, D-ribose and monosaccharideswith carboxyl groups such as D-galacturonic acid.

These monomers and the higher units based on them can also be modifiedby -OSO₃H and/or OPO₃H groups.

Here the fucosylation or sialisation of the carbohydrates can beperformed in the usual way.

As already stated above, the mixture ratio a:b:c can be up to 1:1000:1.This is in particular the case when only little free fucose and/or freesialic acid is present.

The ratio of the total neutral carbohydrates to the total acidcarbohydrates (for example NeuAc and/or carbohydrates with OSO₃H and/orOPO₃H groups should preferably be 00:1 to 1:1, and especially preferably10:1.

The monosaccharides and oligosaccharides used in the mixture accordingto the invention admittedly show a low affinity (binding or complexing)for certain receptors, but owing to the increased diffusion andflexibility can surprisingly decompose already existing complexes ofsubstances and organisms (toxins/viruses, bacteria and cells) with thetarget structures (for example epithelial surfaces) and the recognitionmolecules associated therewith (i.e. receptors).

The polysaccharides present in the mixture according to the inventiondisplay many epitopes (binding sites) and hence possess an affinityseveral orders of magnitude higher and hence strong binding (compared tothe small molecules) to the corresponding receptors. In addition, thoughmolecules with such polyvalent binding sites, a cross-linking of manyrecognition molecules is achieved. Thus these polysaccharides can stablymask substances and organisms, for example bacteria, but in somecircumstances also their receptors and all (epiihelial) surfaces.Adhesion of the substances and organisms, for example bacteria, to cellsurfaces and all the epithelia is thus prevented. In addition, theexclusion or the destruction of the substances and organisms from thebody is furthered.

The fucose and sialic acid units influence the biological activity ofoligo- and polysaccharides.

Below, various carbohydrate mixtures representing preferred embodimentsare described. In this, statements are based on wt %, unless otherwisestated.

EXAMPLE 1

Composition Component Wt % Fucose 0.5 Glucose 0.5 Sialyllactoses 1Fucosyllactoses 0.5 Fucosylated oligosaccharides such as 4Lactofucopentaoses Sialylated oligosaccharides such asDisialolacto-N-tetraose 1 Maltodextrin 72.5 Starch 20

EXAMPLE 2

Composition Component Wt % Fucose 0.5 Glucose 0.5 Sialyllactoses 1Fucosyllactoses 0.5 Fucosylated oligosaccharides such as 4Difucosyl-lactose Sialylated oligosaccharides such asSialolacto-N-hexaoses 1 Inulin 72.5 Starch 20

EXAMPLE 3

Composition Component Wt % Fucose 1.5 Glucose 0.5 Sialyllactoses 1Fucosyllactoses 0.5 Fucosylated oligosaccharides such as 3Difucosyl-lacto-N-tetraose Sialylated oligosaccharides such as 1Disialolacto-N-hexaoses Oligosaccharides such as mannans and 10Galactans Inulin 62.5 Microcrystalline cellulose 20

EXAMPLE 4

Composition Component Wt % Fucose 1.5 Glucose 0.5 Sialyllactoses 1Fucosyllactoses 0.5 Fucosylated oligosaccharides such as 3Lactofucopentaoses Sialylated oligosaccharides such asDisialolacto-N-tetraose 1 Galactooligosaccharides 10 Inulin 62.5Microcrystalline cellulose 20

EXAMPLE 5

Composition Component Wt % Fucose 0.1 Glucose 0.5 Sialyllactose 0.5Fucosyllactoses 4.9 Disialolacto-N-tetraose 2.0 Maltodextrin 70 Starch22

EXAMPLE 6

Composition Component Wt % Fucose 0.1 Glucose 0.5 Sialyllactose 1Fucosyllactoses 0.9 Galacto-oligosaccharides 20.5 Inulin 5 Starch 72

What is claimed is:
 1. Carbohydrate mixture for dietetic, enteral andparenteral foods and also pharmaceuticals, characterised in that it ismade up of a=monosaccharide(s), b=oligosaccharide(s) having 2 to 6monosaccharide units and c=polysacchanide(s) having 7 or moremonosaccharide units with a mixing ratio a:b:c, based on weight, a=1b=40 to 1000 and c=1 to 50, and contains at least 1 wt % fucose in freeform and/or in a form bound to an oligosaccharide and/or apolysaccharide.
 2. Carbohydrate mixture according to claim 1,characterised in that the mixing ratio a:b:c: is ca. 1:80:20. 3.Carbohydrate mixture according to claim 1, characterised in that itcontains at least 5 wt % fucose.
 4. Carbohydrate mixture according toclaim 3, characterised in that it contains from 5 to 10 wt % fucose. 5.Carbohydrate mixture according to claim 1, characterised in that thefucose is bound to the oligosaccharides and polysaccharides as follows:α1-2, α1-3, α1-4, α1-6.
 6. Carbohydrate mixture according to claim 1,characterised in that it contains at least 1 wt % sialic acid(s) in freeform and/or a form bound to an oligosaccharide and/or a polysaccharide.7. Carbohydrate mixture according to claim 6, characterised in that itcontains 1 to 5 wt % sialic acid(s).
 8. Carbohydrate mixture accordingto claim 6 wherein the sialic acid(s) are in bound form as sialyllactoseand/or disialyllactose or disialyllacto-N-tetraose.
 9. Carbohydratemixture according to claim 6 characterised in that the sialic acid(s) is(are) bound to the oligosaccharides as follows: α2-3, α2-6, α2-8. 10.Carbohydrate mixture according to claim 1, characterised in that themonosaccharides essentially consist of the following monomers or theoligosaccharides and polysaccharides are essentially composed of thefollowing monomers, which can be modified by —OSO3H and/or —OPO3Hgroups: N-acetylnerminic acid, N-glycolyineuraminic acid and/orO-acerylated forms thereof, D-glucose, D-fructose, D-galactose,D-mannose, L-fucose, D-N-acetylglucosamine, D-N-acetylgalactosamine,D-xylose, L-rhamnose, D-arabinose, D-allose, D-talose, L-idose, D-riboseand monosaccharides with carboxyl groups.
 11. Carbohydrate mixtureaccording to claim 8 wherein the monosaccharide with a carboxyl group isD-galacturonic acid.
 12. Carbohydrate mixture according to claim 1,characterised in that the monosaccharides, oligosaccharides andpolysaccharides can be or have been fucosylated and optionallysialylated.
 13. A method for prophylaxis and/or treatment ofsymptoms/diseases, which are connected with the association/adhesion ofpathogenic substances and organisms to epithelia or other endogenouscells which comprises administering to an infant in need thereof themixture of claim 1 in an amount of at least 100 mg/kg body weight/day.14. A method for prophylaxis and/or treatment of symptoms/diseases,which are connected with the association/adhesion of pathogenicsubstances and organisms to epithelia or other endogenous cells whichcomprises administering to an infant in need thereof the mixture ofclaim 1 in an amount of about 500 mg/kg body weight/day.
 15. A methodfor prophylaxis and/or treatment of symptoms/diseases, which areconnected with the association/adhesion of pathogenic substances andorganisms to epithella or other endogenous cells which comprisesadministering to an adult in need thereof the mixture of claim 1 in anamount of at least 200 mg/kg body weight/day.
 16. A method forprophylaxis and/or treatment of symptoms/diseases, which are connectedwith the association/adhesion of pathogenic substances and organisms toepithelia or other endogenous cells which comprises administering to anadult in need thereof the mixture of claim 1 in an amount of about 1g/kg body weight/day.